Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation.

INTRODUCTION: The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. METHODS: Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. RESULTS: Peripheral blood was isolated from 266 patients without diabetes mellitus ( n=182), with diabetes mellitus not treated with metformin ( n=34), and with diabetes mellitus actively taking metformin ( n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1ß, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-ß. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. CONCLUSION: Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment.

Surgical margins and primary site resection in achieving local control in oral cancer resections.

OBJECTIVES/HYPOTHESIS: Evaluate effectiveness of resection of oral cavity cancer with a standardized approach for margin evaluation. Primary end points were local control and survival. STUDY DESIGN: Retrospective, nonrandomized, single institution. METHODS: One hundred eight patients who underwent surgery for oral cancer were evaluated using specific anatomical pathology criteria. Frozen section was performed with the surgeon and pathologist agreeing where on the specimen the frozen sections should be taken in most cases. RESULTS: Ninety-one patients (84.3%) had frozen sections taken from the specimen, eight from the tumor bed, and nine had none taken at the time of surgery. Overall local recurrence rate was 18.5%, 25% in patients who had margins taken from the tumor bed and 17.6% when taken from the specimen. Twenty-nine patients had margins ≥5 mm, 53 <5 mm and clear, and 14 positive re-resected to negative with local recurrence rates of 3.4%, 26.4%, and 28.6%, respectively. The radial distance of the resection margin was shown to have an impact on overall survival (hazard ratio [HR] = 3.59, 95% confidence interval [CI] = 1.12-11.57), disease-free survival (HR = 7.00, 95% CI = 1.89-25.95), and local recurrence-free survival (HR = 28.80, 95% CI = 3.00-276.82). CONCLUSIONS: Assessing margins from the resection specimen rather than the tumor bed consistently predicts local control. There is a statistical improvement in local control, disease-free, and overall survival with increasing radial margin distance from the tumor, and 5 mm should be agreed upon as the definition of a clear resection margin. Frozen sections can be used to revise positive or close resection margins intraoperatively with improved outcomes. LEVEL OF EVIDENCE: 4.

Anatomic evaluation of endoscopic transnasal transorbital approach to the lateral orbital apex.

BACKGROUND: This anatomic study investigates the feasibility of an endoscopic transnasal transorbital approach to the lateral orbital apex. METHODS: Five cadavers with no prior history of sinus surgery were studied bilaterally. Standard techniques and instrumentation for functional endoscopic sinus surgery were used to perform dissections and delineate anatomy of sinuses and orbits. RESULTS: With resection of the inferior aspect of the lamina papyracea and the medial portion of the orbital floor, followed by incision of the periorbita along the inferomedial aspect of the orbit and removal of minimal orbital fat, a satisfactory view of the surgical field is achieved. The medial and inferior rectus muscles are dissected and retracted to allow visualization of the optic nerve. By dissecting inferior to the optic nerve and using 0 and 30° endoscopes, the lateral orbital apex could be accessed without damage to the optic nerve. CONCLUSION: In patients whose vision is irreparably damaged, one might consider an endoscopic approach to lesions of the lateral orbital apex. Approach in patients with intact vision should be handled with caution because of possible traction of the optic nerve.